What is the clinical benefit of radiotherapy in metastatic spinal cord compression?
Spinal cord compression occurs in 5-10% of patients with metastatic cancer. Patients can present with pain or neurological deficits such as limb weakness, sensory changes and bowel or bladder dysfunction. Urgent treatment is necessary to prevent progression of neurological deficit which may result in a reduction in functional status.
The diagnosis of spinal cord compression is ideally based on an MRI scan. However, clinical symptoms and signs together with consistent findings on a CT scan may be sufficient for diagnosis.
Clinical benefit of palliative radiotherapy
The two treatment modalities used in the treatment of spinal cord compression are surgery and radiotherapy. There have been no randomised trials comparing the two single modalities.
Patchell (2005) compared the addition of decompressive surgery to radiotherapy with radiotherapy alone in patients with single level spinal cord compression. These patients had <48 hours of paraplegia and an expected life expectancy of three months and included patients with an unstable spine (ie pathological fracture or bone in the spinal canal). One hundred and one patients were randomised to surgery and radiotherapy versus radiotherapy alone. The radiotherapy dose was 30Gy in 10 fractions for both arms. Functional outcomes were significantly better in the surgical arm with a post treatment ambulatory rate of 84% versus 57% and median duration of ambulation 122 days versus 13 days. Of the non-ambulant patients 62% of the surgical group and 19% of the radiotherapy alone group regained the ability to walk. Patients undergoing surgery also had better continence, muscle strength and reduced dexamethasone and analgesic use. However, 18/51 patients in the radiotherapy alone group had unstable spines, which radiotherapy alone would not be expected to fix and could explain the poorer outcomes in this group.
Chen et al conducted a meta-analysis of studies which evaluated surgery (with or without adjuvant radiotherapy) or radiotherapy for metastatic spinal cord compression. All study types were included but there were no randomised controlled trials found. Patients undergoing surgery had significantly improved ambulation (22% vs 12%), better pain relief (89% vs 69%) and better one year survival than those undergoing radiotherapy alone. However results were not reported by primary tumour site, single versus multi-level spinal cord compression or whether or not systemic therapies were used, all of which can impact on functional outcomes and survival.
Surgery is of benefit to those patients who have unstable spines as a result of their cancer. The SINS score has been found to have good inter- and intra-observer reliability for assessing spinal stability. See Table 1. SINS from Fourney et al 2011. A score of 0-6 denotes stability, 7-12 indeterminate stability and 13-18 instability. A surgical consultation is recommended for patients with SINS scores ≥7. Patient factors such as performance status, metastatic tumour burden, suitability for systemic therapies and fitness for anaesthetic should also be taken into account.
For patients treated with radiotherapy alone, there have been two randomised trials of different dose fractionation regimens. Maranzano et al randomised 300 patients with an expected life expectancy greater than six months and no indication for surgery to 16Gy in 2 fractions or a split course of 15Gy in 3 fractions followed by 15Gy in 5 fractions. Two hundred and seventy-six patients were available for analysis and 28% of patients had NSCLC. There were no differences in outcomes between the two schedules. Reduction in pain was seen in 57% of patients, with 24% having a complete response and 33% partial response. Ninety percent of ambulant patients remained ambulant, 35% of non-ambulant patients became ambulant but no paraplegic patients regained the ability to walk. The median duration of improvement was 3.5 months and the median survival was four months. Rades et al randomised 203 patients with no indication for surgery to 20Gy in 5 fractions or 30Gy in 10 fractions. One hundred and fifty-five patients were available for analysis and 37% had lung cancer. There was no significant difference in the measured outcomes between the two arms. The overall response rate at one month after radiotherapy was 88%, with 41% showing an improvement in motor outcomes and 47% no further progression. Seventy-three percent of patients were ambulant at one month after radiotherapy. There was no difference in local progression-free or overall survival.
An international multicentre retrospective study of 1034 patients with spinal cord compression compared different radiotherapy fractionation schemes ie 8Gy in 1 fraction, 20Gy in 5 fractions, 30Gy in 10 fractions, 37.5Gy in 15 fractions and 40Gy in 20 fractions. Fourteen percent of patients had NSCLC. There were no differences in functional outcomes between the radiation regimens. Motor function improved in 26%-31% and post-treatment ambulatory rates ranged from 63-74%. Infield recurrences at two years were higher in the 8 and 20Gy arms compared to the other doses (24-26% versus 7-14%).
Short course radiotherapy (8Gy in 1 fraction, 20Gy in 5 fractions) has been compared to long course radiotherapy (30Gy in 10 fractions, 35.5Gy in 15 fractions, 40Gy in 20 fractions) in patients with spinal cord compression from NSCLC. In this retrospective study of 252 patients there was no difference seen in motor function between the groups. Motor function improved in 13% versus 15%, was unchanged in 53% versus 55% and deteriorated in 34% versus 30% in the long course versus short course arms respectively. Median survival was four months.
The toxicity from these radiotherapy regimens is mild. Maranzano et al reported 1% Gd 3 oesophagitis, 0.5% Gd 3 pharyngeal dysphagia and 3% Gd 3 vomiting. Rades et al reported no toxicities exceeding Grade 2 and no late toxicities, although specific toxicities were not listed.
Evidence summary and recommendations
|Palliative radiotherapy can relieve pain and improve neurological function in patients with spinal cord compression from metastatic cancer.||II||, , |
|For patients treated with radiotherapy alone, lower radiotherapy doses (8Gy/1 fraction, 16Gy/2 fractions, 20Gy/5 fractions) have equivalent ambulatory and functional outcomes compared with higher radiotherapy doses.||II, III-2||, , |
|Decompressive surgery in addition to radiotherapy may improve ambulatory and functional outcomes in selected patients with single level spinal cord compression.||II|||
|Patients who have spinal cord compression from metastatic cancer should be considered for radiotherapy, either as primary treatment or following surgery.||B|
|Recommended radiotherapy doses for patients treated with radiotherapy alone are 8-20Gy in 1-5 fractions.||B|
Patients with spinal cord compression may be commenced on dexamethasone 4-16mg a day to reduce oedema around the spinal cord. This can be weaned once treatment is complete.
Spinal stability should be assessed in patients with spinal cord compression. The SINS score is a useful tool to assess this but patient factors should also be taken into account.
- Patchell RA, Tibbs PA, Regine WF, Payne R, Saris S, Kryscio RJ, et al. Direct decompressive surgical resection in the treatment of spinal cord compression caused by metastatic cancer: a randomised trial. Lancet 2016 May 27;366(9486):643-8 [Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16112300].
- Chen B, Xiao S, Tong X, Xu S, Lin X. Comparison of the therapeutic efficacies of surgery with or without adjuvant radiotherapy versus radiotherapy alone for metastatic spinal cord compression: a meta-analysis. World Neurosurg 2014 Dec 20 [Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/25536156].
- Fourney DR, Frangou EM, Ryken TC, Dipaola CP, Shaffrey CI, Berven SH, et al. Spinal instability neoplastic score: an analysis of reliability and validity from the spine oncology study group. J Clin Oncol 2011 Aug 1;29(22):3072-7 [Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21709187].
- Maranzano E, Bellavita R, Rossi R, De Angelis V, Frattegiani A, Bagnoli R, et al. Short-course versus split-course radiotherapy in metastatic spinal cord compression: results of a phase III, randomized, multicenter trial. J Clin Oncol 2005 May 20;23(15):3358-65 [Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15738534].
- Rades D, Šegedin B, Conde-Moreno AJ, Garcia R, Perpar A, Metz M, et al. Radiotherapy With 4 Gy × 5 Versus 3 Gy × 10 for Metastatic Epidural Spinal Cord Compression: Final Results of the SCORE-2 Trial (ARO 2009/01). J Clin Oncol 2016 Feb 20;34(6):597-602 [Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/26729431].
- Rades D, Stalpers LJ, Schulte R, Veninga T, Basic H, Engenhart-Cabilic R, et al. Defining the appropriate radiotherapy regimen for metastatic spinal cord compression in non-small cell lung cancer patients. Eur J Cancer 2006 May;42(8):1052-6 [Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16580192].